Replies to post #389316 on NorthWest Biotherapeutics Inc (NWBO)

[hankmanhub]

In short, the WHO re-classifications do not make a lot of difference in the case of our trial. L remains the best treatment prospect for the 95% wild-type, precisely because it is fully personalised, and it will probably be best for the 5% mutated IDH as well.
And there is no reason why regulators shouldn't see it this way.

THIS WAS EXACTLY THE POINT I WAS TRYING TO MAKE IN MY PREVIOUS POSTS.

[ATLnsider]

longfellow95, I agree with everything you said.

The only thing I would add is, I also believe that after DCVax-L is approved, and it becomes a core / foundational part of the new standard of care (SOC) to treat both ndGBM and rGBM, adjuvant DCVax-L will be combined with a neoadjuvant PD-1 inhibitor (Keytruda / Pembrolizumab) treatment.

The PD-1 inhibitor will be given to the GBM patients prior to their tumor resection surgery. Then, after the GBM patients recover from their tumor resection surgery, they will receive an adjuvant treatment of DCVax-L.

[Chiugray]

And mutated IDH goes with younger age, better prognosis, and a pro-neural signature. But we are only talking about roughly 5% of the GBM population (the 5% that will no longer be called GBM).

Thanks for the great explanation. Could this 5% be correlated with the overall survival stat of roughly 5% for GBM patients alive at 5 years? I'm thinking, 95% of GBM patients never had an effective treatment. If for all of this time, the SOC (surgery, radiation, chemo) only worked on 5% of the GBM patient population (now no longer GBM LOL), then the narrative for a successful DCVAX-L is very different. DCVAX-L would be a first ever effective SOC treatment, period, not a replacement SOC.

Also, if the reason the current SOC works on the 5% only is because IDH mutant makes cancer cells more susceptible to chemo and not the case for the 95% (mesenchymal, primarily IDH wild type), then maybe the we can do away with chemo altogether for the 95% of GBM patients.

[sentiment_stocks]

Excellent to hear from you as it was through you that I'd learned about the wild-type and mutated IDH in the first place, and your post confirms all that.

Additionally, L will almost certainly be the most effective option by far, for rGBM patients who weren't able to receive L at the time of initial diagnosis. (Kristyn's Dad is only here because of L.

To this point, another topic to consider is that should the control arm of the L trial that had crossed over, compare well statistically to the external control arms of other trials, that efficacy will be reflective of a positive outcome having used the original tumor from the initial diagnosis... and NOT, having used the tumor that had developed upon progression.

And many of us already know and have discussed ad nauseam about how, upon recurrence, GBM usually transitions to a more mesenchymal (works really well with DCVax-L) sub-type.

Therefore, it would be logical...
especially when comparing the success of other compassionate use types (such as Kat and Kristyn's dad) that had received L using their RECURRENT tumor (and not on the original tumor)...
that for a recurrent GBM patient, a positive prognosis is even more likely when DCVax-L is made with the recurrent tumor.

[flipper44]

Dr. Liau herself has encouraged idh mutant tumor patients to pursue other options, and Dr. Prins and Dr. Liau have long thought Proneural (aka idh mutant) is likely less responsive to DCVax-l. Also, it seems a bit cavalier to suggest the reclassification of GBM now excluding idh (and H3) mutant will not have impact on DCVax-l’s trial interpretations and every other GBM trial for that matter. It’s a big deal.

GBM, as it is now internationally defined, will be more responsive to DCVax-l than GBM as it was previously defined.

It’s that simple. IMO.

[Know-Fear]

Cool. Does make one wonder how long the WHO re-classification was in the works? And noting the re-classification does not make a lot of difference for the L trial. With all things being equal probably best the journal publication is subsequent WHO re-classification……Not to imply anything beyond random thinking of the late night variety.

[eagle8]

Thank you longfellow for this excellent presentation on the primary GBM
and mutants of GBM a.k.a mesenchymal, IDHwt and pro neural IDHm.

Best to you.

[CaptainObvious]

Longfellow, thanks for this great post.

[hyperopia]

Nice post longfellow. This landmark trial should set a new standard, and I think part of the reason for the collection of the IDH mutation data is that future trials in Glioblastoma will now be compared to this new standard. This is from the last time the WHO reclassified brain tumors in 2016, but is still relevant:

World Health Organization Reclassification of Brain Tumors Overview & Frequently Asked Questions (FAQ)

1. Why are these changes happening now?
?The World Health Organization sets international standards for how tumors are classified, and in conjunction with leaders in each field, periodically review their classifications to ensure that the latest science is guiding how tumors are defined. Recent findings from brain tumor research studies in the past few years have provided new information on the distinct molecular make-up of many brain tumor types, as well as how some types that look different under a microscope may actually be driven by the same mutations, and thus behave the same way...or, conversely, that two current types look the same under a microscope, but have very different genetic alterations, and thus should be treated differently.

2. Why does it matter how tumors are defined? Why does re-classification matter?
How tumors are classified – or defined, or characterized – has an impact on many different and important aspects of individual, as well as population, health in any given disease area. This includes:

* Care of individual patients – more accurate diagnosis, estimating prognosis, guiding therapy
* Conduct and interpretation of clinical trials – ensure that patients participating in clinical trials are comparable within and across trials
* Stratification for future clinical trials – matching patients by their molecular signatures with target therapies most likely to benefit them
* Getting the right results from scientific experiments – more accurate analysis and understanding of experimental studies in the lab
* Disease epidemiology- better interpretation of population-based disease trends that may help identify causes and risk factors
* Research funding- allocation of resources by governments and health insurers to support health care based on areas of greatest need

http://braintumor.org/wp-content/assets/WHO-Re-Classification-2016_FINAL.pdf